Forskning ved Københavns Universitet - Københavns Universitet

Forside

Stress-induced cell death is mediated by ceramide synthesis in Neurospora crassa

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Standard

Stress-induced cell death is mediated by ceramide synthesis in Neurospora crassa. / Plesofsky, Nora S; Levery, Steven B; Castle, Sherry A; Brambl, Robert.

I: Eukaryotic Cell, Bind 7, Nr. 12, 01.12.2008, s. 2147-59.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Plesofsky, NS, Levery, SB, Castle, SA & Brambl, R 2008, 'Stress-induced cell death is mediated by ceramide synthesis in Neurospora crassa', Eukaryotic Cell, bind 7, nr. 12, s. 2147-59. https://doi.org/10.1128/EC.00147-08

APA

Plesofsky, N. S., Levery, S. B., Castle, S. A., & Brambl, R. (2008). Stress-induced cell death is mediated by ceramide synthesis in Neurospora crassa. Eukaryotic Cell, 7(12), 2147-59. https://doi.org/10.1128/EC.00147-08

Vancouver

Plesofsky NS, Levery SB, Castle SA, Brambl R. Stress-induced cell death is mediated by ceramide synthesis in Neurospora crassa. Eukaryotic Cell. 2008 dec 1;7(12):2147-59. https://doi.org/10.1128/EC.00147-08

Author

Plesofsky, Nora S ; Levery, Steven B ; Castle, Sherry A ; Brambl, Robert. / Stress-induced cell death is mediated by ceramide synthesis in Neurospora crassa. I: Eukaryotic Cell. 2008 ; Bind 7, Nr. 12. s. 2147-59.

Bibtex

@article{0e44f7e3b6e944d38db5fd55795295b3,
title = "Stress-induced cell death is mediated by ceramide synthesis in Neurospora crassa",
abstract = "The combined stresses of moderate heat shock (45 degrees C) and analog-induced glucose deprivation constitute a lethal stress for Neurospora crassa. We found that this cell death requires fatty acid synthesis and the cofactor biotin. In the absence of the cofactor, the stressed cells are particularly sensitive to exogenous ceramide, which is lethal at low concentrations. When we extracted endogenous sphingolipids, we found that unique ceramides were induced (i) by the inhibitory glucose analog 2-deoxyglucose and (ii) by combined heat shock and 2-deoxyglucose. We determined that the former is a 2-deoxyglucose-modified ceramide. By structural analysis, we identified the latter, induced by dual stress, as C(18)(OH)-phytoceramide. We also identified C(24)(OH)-phytoceramide as a constitutive ceramide that continues to be produced during the combined stresses. The unusual C(18)(OH)-phytoceramide is not made by germinating asexual spores subjected to the same heat and carbon stress. Since these spores, unlike growing cells, do not die from the stresses, this suggests a possible connection between synthesis of the dual-stress-induced ceramide and cell death. This connection is supported by the finding that a (dihydro)ceramide synthase inhibitor, australifungin, renders cells resistant to death from these stresses. The OS-2 mitogen-activated protein kinase, homologous to mammalian p38, may be involved in the cell death signaling pathway. Strains lacking OS-2 survived the combined stresses better than the wild type, and phosphorylated OS-2 increased in wild-type cells in response to heat shock and combined heat and carbon stress.",
keywords = "Ceramides, Lipids, Neurospora crassa, Spectrometry, Mass, Electrospray Ionization",
author = "Plesofsky, {Nora S} and Levery, {Steven B} and Castle, {Sherry A} and Robert Brambl",
year = "2008",
month = dec,
day = "1",
doi = "10.1128/EC.00147-08",
language = "English",
volume = "7",
pages = "2147--59",
journal = "mSphere",
issn = "2379-5042",
publisher = "American Society for Microbiology",
number = "12",

}

RIS

TY - JOUR

T1 - Stress-induced cell death is mediated by ceramide synthesis in Neurospora crassa

AU - Plesofsky, Nora S

AU - Levery, Steven B

AU - Castle, Sherry A

AU - Brambl, Robert

PY - 2008/12/1

Y1 - 2008/12/1

N2 - The combined stresses of moderate heat shock (45 degrees C) and analog-induced glucose deprivation constitute a lethal stress for Neurospora crassa. We found that this cell death requires fatty acid synthesis and the cofactor biotin. In the absence of the cofactor, the stressed cells are particularly sensitive to exogenous ceramide, which is lethal at low concentrations. When we extracted endogenous sphingolipids, we found that unique ceramides were induced (i) by the inhibitory glucose analog 2-deoxyglucose and (ii) by combined heat shock and 2-deoxyglucose. We determined that the former is a 2-deoxyglucose-modified ceramide. By structural analysis, we identified the latter, induced by dual stress, as C(18)(OH)-phytoceramide. We also identified C(24)(OH)-phytoceramide as a constitutive ceramide that continues to be produced during the combined stresses. The unusual C(18)(OH)-phytoceramide is not made by germinating asexual spores subjected to the same heat and carbon stress. Since these spores, unlike growing cells, do not die from the stresses, this suggests a possible connection between synthesis of the dual-stress-induced ceramide and cell death. This connection is supported by the finding that a (dihydro)ceramide synthase inhibitor, australifungin, renders cells resistant to death from these stresses. The OS-2 mitogen-activated protein kinase, homologous to mammalian p38, may be involved in the cell death signaling pathway. Strains lacking OS-2 survived the combined stresses better than the wild type, and phosphorylated OS-2 increased in wild-type cells in response to heat shock and combined heat and carbon stress.

AB - The combined stresses of moderate heat shock (45 degrees C) and analog-induced glucose deprivation constitute a lethal stress for Neurospora crassa. We found that this cell death requires fatty acid synthesis and the cofactor biotin. In the absence of the cofactor, the stressed cells are particularly sensitive to exogenous ceramide, which is lethal at low concentrations. When we extracted endogenous sphingolipids, we found that unique ceramides were induced (i) by the inhibitory glucose analog 2-deoxyglucose and (ii) by combined heat shock and 2-deoxyglucose. We determined that the former is a 2-deoxyglucose-modified ceramide. By structural analysis, we identified the latter, induced by dual stress, as C(18)(OH)-phytoceramide. We also identified C(24)(OH)-phytoceramide as a constitutive ceramide that continues to be produced during the combined stresses. The unusual C(18)(OH)-phytoceramide is not made by germinating asexual spores subjected to the same heat and carbon stress. Since these spores, unlike growing cells, do not die from the stresses, this suggests a possible connection between synthesis of the dual-stress-induced ceramide and cell death. This connection is supported by the finding that a (dihydro)ceramide synthase inhibitor, australifungin, renders cells resistant to death from these stresses. The OS-2 mitogen-activated protein kinase, homologous to mammalian p38, may be involved in the cell death signaling pathway. Strains lacking OS-2 survived the combined stresses better than the wild type, and phosphorylated OS-2 increased in wild-type cells in response to heat shock and combined heat and carbon stress.

KW - Ceramides

KW - Lipids

KW - Neurospora crassa

KW - Spectrometry, Mass, Electrospray Ionization

U2 - 10.1128/EC.00147-08

DO - 10.1128/EC.00147-08

M3 - Journal article

C2 - 18952903

VL - 7

SP - 2147

EP - 2159

JO - mSphere

JF - mSphere

SN - 2379-5042

IS - 12

ER -

ID: 33752123